Spiegelhalder B, Preussmann R
Carcinogenesis. 1985 Apr;6(4):545-8. doi: 10.1093/carcin/6.4.545.
Under normal conditions a possible N-nitrosodimethylamine formation in vivo cannot directly be monitored in urine due to high metabolic conversion rate (greater than 99.9%). Own experiments showed an increased excretion rate (up to 2.4%) if ethanol was administered simultaneously. This model was used for monitoring experiments with respect to in vivo formation of N-nitrosodimethylamine. Amidopyrine, as a compound which is easily nitrosated, was administered (single oral dose of 500 mg) to volunteers. Under the influence of 20-30 g ethanol it was possible to detect N-nitrosodimethylamine in urine. From negative control experiments it must be concluded that this appearance of N-nitrosodimethylamine derives from in vivo nitrosation of the drug. The amount excreted in urine varied between 0.5 and 10 micrograms N-nitrosodimethylamine within 8 h and seemed to be influenced by salivary nitrite concentrations which ranged from 5 to 220 p.p.m. NO-2. In comparison with earlier excretion studies in humans it can be assumed that only 1-2% of the originally formed nitrosamine was found in urine. To our knowledge this is the first time that in vivo formation of N-nitrosodimethylamine was directly shown to occur in humans.
在正常情况下，由于体内代谢转化率高（大于99.9%），无法直接通过尿液监测体内可能形成的N-亚硝基二甲胺。我们自己的实验表明，如果同时给予乙醇，排泄率会增加（高达2.4%）。该模型用于监测N-亚硝基二甲胺体内形成的实验。将易被亚硝化的氨基比林（单次口服剂量500毫克）给予志愿者。在20 - 30克乙醇的影响下，能够在尿液中检测到N-亚硝基二甲胺。从阴性对照实验可以得出结论，N-亚硝基二甲胺的这种出现源于药物的体内亚硝化。8小时内尿液中排泄的N-亚硝基二甲胺量在0.5至10微克之间，似乎受唾液中亚硝酸盐浓度的影响，唾液中亚硝酸盐浓度范围为5至220 ppm NO₂。与早期人类排泄研究相比，可以假设在尿液中仅发现了最初形成的亚硝胺的1 - 2%。据我们所知，这是首次直接证明人类体内会发生N-亚硝基二甲胺的形成。
